biomedicines Review Learning and Unlearning of Pain Larissa Cordier and Martin Diers * ID Department of Psychosomatic Medicine and Psychotherapy, LWL University Hospital, Ruhr University Bochum, 44791 Bochum, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-234-5077-3175 Received: 17 April 2018; Accepted: 1 June 2018; Published: 5 June 2018 Abstract: This review provides an overview of learning mechanisms and memory aspects for the development of chronic pain. Pain can be influenced in important ways by an individual’s personality, by family, and by the sociocultural environment in which they live. Therefore, learning mechanisms can explain why pain experience and pain behavior can increase or decrease. Linking pain with positive consequences or removing negative consequences can contribute significantly to the chronification of pain. We will provide an overview of treatment options that use the characteristics of extinction. Operant extinction training and cognitive behavioral approaches show promising results for the treatment of chronic pain. Keywords: chronic pain; learning; classical conditioning; operant conditioning; observational learning; extinction; operant behavioral treatment; cognitive behavioral treatment 1. Introduction Learning mechanisms are a basic concept in behavioral medicine. There are different mechanisms involved in learning, such as classical and operant conditioning, extinction, habituation, and sensitization. Classical conditioning is a learning procedure in which a biological potent stimulus is paired with a former neutral stimulus. As a result of the pairing, the neutral stimulus elects a response without the biological potent stimulus. Ivan Pavlov, who conditioned a salivation response to the sound of a bell, first described this learning procedure [1]. Whenever he fed his dog, he rang a bell and gave him food. After some time, the dogs salivation was present just by ringing the bell without presenting the food. Another learning procedure is operant conditioning. This procedure is characterized by the fact that the behavior is modified by reinforcement or punishment. During this learning process, an association is made between a behavior and a consequence for that behavior [2]. For example, when someone trains a dog to fetch a ball, he praises him and pats him on the head whenever the dog performs the correct behavior. But if the dog is grubbing a flower bed, he will be punished to reduce this kind of behavior. The question arises as to whether it is possible to reverse the learning process and unlearn a behavior. This process is called extinction and it can be used to unlearn classical or operant conditioned behavior [3]. If Pavlov’s dog hears a bell but no food occurs, the association between these stimuli will weaken, or if someone forgets to praise and pat the dog, he will show less of the desired behavior. However, extinction is not the same as oblivion. Learning can also be gained through observation and replication of other behavior. Albert Bandura [4] adds two ideas to the principals of behavioral learning theories: 1. mediating processes occur between stimuli and responses; and 2. behavior is learned from the environment through the process of observational learning. In a famous study by Bandura [5], children observed the behavior of an adult dealing with a doll. After the children were left alone with the doll, they imitated the seen behavior of the adults. Biomedicines 2018, 6, 67; doi:10.3390/biomedicines6020067 www.mdpi.com/journal/biomedicines Biomedicines 2018, 6, 67 2 of 7 Is it possible to adapt to stimuli without explicitly responding to them? According to Groves and Thompson, these learning mechanisms rely on two processes: habituation and sensitization [6]. Habituation occurs if someone no longer notices a stimulus that is repeatedly presented without a reward, punishment, or change in intensity [7]. For example, someone lives in an apartment next to a train station. At the beginning, he perceives the train noises as annoying and hears every motion of the train, but after some time, the person adapts to the noises and will not hear them anymore. The opposite of habituation is sensitization. Sensitization refers to the increase in the strength of a reaction with repeated presentation of the same stimulus. Even though both processes are not conscious, they interact to help people understand their surroundings by strengthening some stimuli and diminishing others [6,8]. However, it has to be noted that all learning mechanisms and behaviors described above can be influenced in important ways by an individual’s personality, family, and the sociocultural environment. Pain Pain is an important evolutionary response signaling danger to the body and triggering protective responses. There is a distinction between acute and chronic pain. Acute pain is usually the reaction to stimulation, has a direct cause, and fulfills an adaptive signal function, whereas chronic pain (duration of at least 3–6 months and/or exceeding the usual healing time for acute injuries) conditions often have no direct cause of pain. After chronification, the pain has lost its basic positive function and becomes an independent disease, which is associated with significant limitations and requires special treatment [9]. If someone suffers from a chronic disease, such as chronic pain, this chronic disease is often associated with a great burden. This burden can result from the disease itself, but also from the associated diagnostic and medical therapeutic measures. The uncertainty about the future of living with this chronic disease can be a particularly strong stressor [9]. 2. Learning Mechanisms 2.1. Operant Learning The most influential psychological model for the chronification of pain was the assumption of Fordyce [10,11]. Chronic pain can get worse by pain behavior. Fordyce postulated that acute pain behavior, such as moaning or hobbling, under the control of an external amplifiercould strengthen the pain and contribute to its chronification. The learning mechanisms behind this process are positive reinforcement (e.g., attention or the expression of pity), negative reinforcement of pain behavior (e.g., adopting a pain relieving posture), and a lack of reinforcement of healthy behavior (e.g., physical activity). These learning processes can maintain chronic pain, even in the absence of a nociceptive influx. Linking pain with positive consequences or removing negative consequences leads to increased pain behavior at all levels (e.g., work, leisure, and family) and can contribute significantly to the chronification of pain [10–12]. Pain behavior, originally induced by nociceptive processes, can occur because of learned environmental contingencies. This model has generated a lot of research; not only have Fordyce’s original assumptions been confirmed, but research was also able to prove that pain sensation and physiological processes of pain processing are operant conditioned. Caregivers, who have a high amplifier potential, play an important role. The reaction towards people who suffer from pain can be divided into three different types: those who reinforce the pain (e.g., expression of compassion, solicitous responses, attention), those who try to distract them from pain (e.g., taking a walk), and those who ignore them (e.g., go out of the room) [13,14]. In a test situation, the pain behavior of chronic pain patients depended on the presence or absence and the reinforcement pattern of their significant other. When the significant other showed comforting and caring behavior towards the chronic pain patient, the pain increased in contrast to a situation without the significant other [13]. Findings by Prenevost and Reme [15] also underline the importance of a significant other on pain coping strategies. During the process of dealing Biomedicines 2018, 6, 67 3 of 7 with pain, the interaction between the significant other and the pain patient is an important underlying factor. The significant other is also relevant for the unlearning of pain and in handling its life changing consequences [16,17]. Equally important are conditioning processes of taking pain medication. Patients often hear from their doctors or well-meaning family members that they should take painkillers if the pain is really strong and they ‘need’ the medication. Patients learn to associate high perceived pain with medication intake. The pain might be reduced in the beginning, but along the way the amount of medication and the frequency of medication intake will increase, leading to medication abuse or dependency. For the effectiveness of a certain pain medication, however, a constant plasma level might be needed. Thus, both behavioral therapists and physicians/pharmacologists recommend a time-contingent medication intake, instead of a pain-contingent medication intake. This means the medication should be taken at fixed times of the day, independent from the pain intensity [18]. The negative reinforcement of the activity level is also an important process in the development of disability. If a specific physical activity—for example, walking—is performed until the occurrence of pain, the patient has to interrupt the activity and rest until the pain decreases. As a result, the patient learns that a reduction of activity reduces pain, leading to lower activity levels and, consequently, muscle atrophy. Therefore, it is necessary that activities are interrupted before they elicit pain. Therefore, the 80% rule is used. Patients should count how